Biopharmaceuticals: the clinical significance

Fossil fuels have been the primary energy source for society since the Industrial Revolution. They provide the raw material for the manufacture of many everyday products that we take for granted, including pharmaceuticals, food and drink, materials, plastics and personal care.
As the 21st century progresses we need solutions for the manufacture of chemicals that are smarter, more predictable and more sustainable.
Industrial biotechnology is changing how we manufacture chemicals and materials, as well as providing us with a source of renewable energy. It is at the core of sustainable manufacturing processes and an attractive alternative to traditional manufacturing technologies to commercially advance and transform priority industrial sectors yielding more and more viable solutions for our environment in the form of new chemicals, new materials and bioenergy.
This course will cover the key enabling technologies that underpin biotechnology research including enzyme discovery and engineering, systems and synthetic biology and biochemical and process engineering. Much of this material will be delivered through lectures to ensure that you have a solid foundation in these key areas. We will also consider the wider issues involved in sustainable manufacturing including responsible research innovation and bioethics.
In the second part of the course we will look at how these technologies translate into real world applications which benefit society and impact our everyday lives. This will include input from our industry stakeholders and collaborators working in the pharmaceutical, chemicals and biofuels industries.
By the end of this course you will be able to:
1. Understand enzymatic function and catalysis.
2. Explain the technologies and methodologies underpinning systems and synthetic biology.
3. Explain the diversity of synthetic biology application and discuss the different ethical and regulatory/governance challenges involved in this research.
4. Understand the principles and role of bioprocessing and biochemical engineering in industrial biotechnology.
5. Have an informed discussion of the key enabling technologies underpinning research in industrial biotechnology
6. Give examples of industrial biotechnology products and processes and their application in healthcare, agriculture, fine chemicals, energy and the environment.

XL

Synthetic biology, industrial fermentation and green chemistry are integrated into the course and it is well organized and is a nice interdisciplinary course.\n\nThanks.

JN

May 21, 2018

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The lectures were divided into modules that were appropriate in length/tie. Speakers were very easy to comprehend and the outline of the topics were well presented.

從本節課中

Case Studies: Glycoscience and Biotherapeutics

Glycoscience is the science and technology of carbohydrates, which are the most abundant biological molecules on Earth and make up part of the biology of all living organisms. This module will introduce the fundamental concepts of glycoscience, leading onto the benefits for society and how this drives and impacts the bioeconomy. A series of case studies will be used to present some of the key challenges and glycan-based solutions in pharmaceuticals and personalised medicine, food security and biomaterials.
Biopharmaceuticals are new medicines that are made biologically. “Biologically” means that the production is too complex for simple chemistry and that we currently have to direct biological materials – cells, using the spectrum of natural catalytic reactions - to make these revolutionary medicines. We will be looking at the revolution in these development medicines within a clinical, societal and economic context and the approaches used to ensure production of safe and effective biopharmaceuticals, using various types of expression systems. Students will be introduced to detailed case studies that illustrate how the principles developed in other sub-modules are put into practice in the industrial context.

教學方

Prof. Nicholas Turner

Deputy Director

Prof. Nigel Scrutton

Director

腳本

Well, hello everyone. What I'd like to do now is to take you to the first actual module on biopharmaceuticals. There's some definitions that I think it's worth our while starting with. The idea that biopharmaceuticals represent natural biological medicines has been well established now. And initially they were purified from biological sources. As you can see in the white column on the right hand side, these are complex. They're generally protein-based molecules and they're made by genetic engineering, sometimes referred to recombinant medicines. They rely on a lot of the technology that's come about through nucleic acid handling. Today, these medicines are harvested from genetically engineered cell-based systems and have alternative names. They may be referred to as biopharmaceuticals but equally they're also called biotherapeutics or sometimes biologics or biologicals and sometimes it's biomedicines. They're made in a process in cells which are almost used as factories to redirect starting materials carrying out a process of fermentation where the cells grow. They're fed by various nutrients and grow to large scale producing then in a manufacturing process, either individually or in combination, processes which together generate the desired output, which is the biological medicine. The steps of bioprocessing are many. It involves not just the production, but also the recovery of molecules, the purification, the verification for quality, and the packaging into a delivery format that can be used as a medicine. Now the great driving force behind the production biopharmaceuticals is the way they can be used for diagnosis, and for treatment of otherwise intractable disease. Diseases that cannot be treated by any other format. And you may well be aware of some of these diseases. For example insulin is used to treat diabetes, more correctly referred to as diabetes mellitus of type one and type two diabetes. The way in which growth hormone is used to treat dwarfism and follicle stimulating hormone is used in infertility therapies. You may also be aware of kidney failure being treated by erythropoietin, also used for other anemias. And there's a series of other diseases involving blood clotting deficiencies. Hemophilia sometimes referred to, where proteins or enzymes that are used to get the correct blood clotting facility are produced to treat patients and there are different types such as Factor VIII, Factor IX and other proteins referred to as Von Willebrand factors. But largely, the therapeutic treatment today is for autoimmune diseases and cancers, where antibodies, immunoglobulins natural protective molecules have been used as therapeutics and for diagnostics in the treatment and identification of disease. To give you one example of that, we can look at the breast cancer therapies, in which breast cancer today is recognized to be due to at least two different underlying causes, one of which is an intracellular mechanism whereby a receptor for a natural hormonal steroid is overexpressed, and it leads to high extensive cell growth in an uncontrolled manner. That's referred to a HER-2 negative. The HER-2 positive form is where a receptor is mutated on the surface of the cell and it drives that whole cell's growth process in an unregulated way. On the HER-2 positive is diagnosed and treated by an antibody that binds to and inhibits the growth factor receptor. This therapy, HER-2 human epidermal growth factor receptor, is a treatment that's been used in about 20% of all therapies where individuals are HER-2 positive and the antibody produced, herceptin, is one of the largest selling biological medicines at present. There's one example that perhaps will be within common knowledge, and something that you would know about. We have in the history part here, a whole series of natural products. Initially, things were purified from human or other animal material. For example, insulin for human therapy came from purified pig pancreas, abattoir material. But there's real concerns about the unknown impurities there. For example, human cadaver-derived pituitary growth hormone and the presence of prions leading to blood-derived clotting factors and HIV. This over the years has driven us away from trying to purify these materials to moving to genetically engineered versions made in cell-based production systems in the bioprocessing format. The amount, the purity and the certainty is a much more available and the quality makes this a much more consistent and robust process. And in addition, we have, moving away from natural products, to genetically engineer molecules of totally different format that have enhanced properties. And by gene manipulation we're generating next generation products and we'll come to that in later modules. How important are these to you? Well these are the materials that appear in the media daily. To give you some leads, just helps you to illustrate the importance to us all. I mean, 10% of us today are diabetics and this is a number that's increasing as we all get older. The prevalence of a type 2 diabetes, also called old age diabetes, is increasing, and the ability to treat such individuals with insulin is helping to prevent obesity, heart disease, blindness, kidney disease, and circulatory conditions. This is something which is really very much, for an aging healthy population, a key factor for treatment. But the engineered antibodies are producing novel therapeutics to treat many cancers and inflammatory diseases. Second generation antibodies, such as Cimzia and Avastin can be life-changing, but the complex molecules and the development manufacture time is time-consuming. It takes about 8-12 years for a successful therapeutic development and this makes them very expensive molecules. You can imagine that if we're to use these as therapeutics to go into humans, we need to make sure that are of a quality, that can be assigned to be safe and to be without serious or toxic risks. There are a number of regulatory agencies operating in different countries, such as the US-based Food and Drug Administration and the European Medicines Agency. The role of those agencies are to ensure the potential therapeutics are as safe as possible, to understand the risk versus the benefit and to provide a forum for advice and expectation across the industrial sector. All companies that are making biopharmaceuticals have to make submissions to the appropriate regulatory agency before a new therapeutic can get on the market. And that comes around from a series of clinical testings, where patients and groups of patients and groups of healthy individuals are subject to treatment to ensure that the therapeutics are safe for intake. Now of course, as a final aspect for us to consider here in the general significance, the sales of biopharmaceuticals are quite immense. In 2013, $140 billion was spent by the purchase of biopharmaceuticals by various agencies, and there's been a year on year increase in expenditure in this area over 15 years. And, although the pharmaceutical market is critically important, 7 of the top 10 selling pharmaceuticals in 2013, were the biopharmaceuticals, with Humira, an antibody used in treatment of diseases such as Rheumatoid Arthritis and Crohn's disease, having sales itself in the region of 11 billion. This is a multinational large business. And companies taking part in this business are global, they have parts of their company in one nation, and other parts in others. This is a highly competitive area as well, the success rate biosimilars, molecules that are copies of originators. And we're having to match the needs of the health providers in terms of cost, when it takes eight to 12 years to develop, and a lots of funding to develop a medicine, we have to try make this economically viable for patient therapeutics. As a summary then for this module. Biopharmaceuticals are complex biological molecules that offer innovative therapies. Today, they're mainly produced from expression of designed recombinant genes, and they're made using cells, natural cells as factories to harness the cellular processes that will convert precursors into these biological molecules. The biopharmaceuticals bioprocessing sector, both industrial and academic, is a commercial success that shows application of biotechnology, the basic biology and manipulation of biological systems for commercial societal and economic use, and it's still evolving to generate therapeutics and therapies that are used in biological innovation. Additionally, it's having to adapt to the financial pressures of the needs of society, treating individuals in a commercially and economically able means.